Methods, systems and devices for treating hypertension

ABSTRACT

Provided is a method of treating arterial hypertension in a patient. The method comprises selecting a patient suffering from arterial hypertension and creating a flow pathway between a first vascular location and a second vascular location. The first vascular location comprises a source of arterial blood and the second vascular location comprises a source of venous blood. The method causes a reduction in diastolic pressure and a reduction in systolic pressure; and the reduction in diastolic pressure is to an extent at least approximating the reduction in systolic pressure. Systems and devices for creating a flow pathway are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of International Patent ApplicationNo. PCT/US2013/062458 (Attorney Docket No. 29919-710.601), filed Sep.27, 2013, which claims the benefit of U.S. Provisional Application No.61/707,280 (Attorney Docket No. 29919-710.101), entitled Methods,Systems and Devices for Treating Hypertension, filed Sep. 28, 2012, theentire contents of which are incorporated herein by reference in theirentirety. This application is related to: U.S. Pat. No. 7,828,814,entitled “Device and Method for Establishing an ArtificialArterio-Venous Fistula”, filed Apr. 4, 2007; U.S. Non-Provisionalapplication Ser. No. 11/152,621, entitled “Devices for Arterio-VenousFistula Creation”, filed Jun. 13, 2005; U.S. Non-Provisional applicationSer. No. 11/151,802, entitled “Methods for Providing Oxygenated blood toVenous Circulation”, filed Jun. 13, 2005; U.S. Non-Provisionalapplication Ser. No. 11/946,454, entitled “Devices, Systems, and Methodsfor Creation of a Peripherally Located Fistula”, filed Nov. 28, 2007;U.S. Non-Provisional application Ser. No. 12/017,437, entitled “Devices,Systems, and Methods for Peripheral Arteriovenous Fistula Creation”,filed Jan. 22, 2008; U.S. Non-Provisional application Ser. No.12/752,397, entitled “Device and Method for Establishing an ArtificialArteriovenous Fistula”, filed Apr. 1, 2010; U.S. Non-Provisionalapplication Ser. No. 12/905,412, entitled “Devices, Systems, and Methodsfor Enhanced Visualization of the Anatomy of a Patient”, filed Oct. 15,2010; the contents of each are incorporated by reference in theirentirety.

TECHNICAL FIELD

The embodiments disclosed herein relate generally to systems, devicesand methods for treating a patient, particularly a patient afflictedwith arterial hypertension.

BACKGROUND

Hypertension is a chronic medical condition in which the blood pressurein the arteries is elevated requiring the heart to work harder tocirculate blood through the vessels. Blood pressure includes twomeasurements, systolic and diastolic, which depend on whether the heartmuscle is contracting (systole) or relaxed between beats (diastole).Normal blood pressure at rest is within the range of 100-400 mmHgsystolic and 60-90 mmHg diastolic. High blood pressure is typicallypresent if it is persistently at or above 140/90 mmHg.

Hypertension is a major risk factor for stroke, myocardial infarction,heart failure, aneurysms of the arteries such as aortic aneurysms,peripheral arterial disease, and is a cause of chronic kidney disease.Even moderate elevation of arterial blood pressure is associated with ashortened life expectancy.

Current treatment methods, such as the administration of pharmaceuticalsand renal denervation therapy, are associated with incomplete orotherwise limited treatment; high cost; invasiveness; and numerousundesirable side effects. There is therefore a need for improvedapproaches, including both devices and methods, for treating patientssuffering from hypertension.

SUMMARY

According to one aspect of the present inventive concepts, a method fortreating hypertension in a patient comprises selecting a patientsuffering from arterial hypertension and creating a flow pathway betweena first vascular location and a second vascular location, where thefirst vascular location comprises a source of arterial blood and thesecond vascular location comprises a source of venous blood, where themethod is constructed and arranged to cause a reduction in diastolicpressure and a reduction in systolic pressure, and where the reductionin diastolic pressure is to an extent at least approximating thereduction in systolic pressure. Arterial hypertension can comprisesystemic arterial hypertension.

The method can be further constructed and arranged to treat a patientdisease or disorder selected from the group consisting of: chronicobstructive pulmonary disease, congestive heart failure, lung fibrosis,adult respiratory distress syndrome; lymphangioleiomytosis; pulmonaryhypertension; sleep apnea such as sleep apnea due to hypoxemia orhypertension; and combinations of these.

The method can be constructed and arranged to cause a decrease invascular resistance, for example a decrease in peripheral vascularresistance such as infrarenal vascular resistance. The method can befurther constructed and arranged to cause a physiologic change in thepatient selected from the group consisting of: increased oxygen deliveryby the arterial system; increased blood volume; increased proportion ofblood flow to the descending aorta; increased blood flow to the kidneys;increased blood flow outside the kidneys; increased cardiac output; andcombinations of these. The method can be further constructed andarranged to minimize chronic increase in heart rate. The method can befurther constructed and arranged to minimize a decrease in cardiacfunction. The method can be further constructed and arranged to minimizeadverse effects to a kidney of the patient. The method can be furtherconstructed and arranged to cause at least one of an increase inoxygenation or an increase in flow rates associated with the patient'schemo-receptors. The method can be further constructed and arranged tomodify the patient's central sympathetic tone. The modification to thepatient's central sympathetic tone can cause a reduction in at least oneof systolic or diastolic blood pressure. The modification to thepatient's central sympathetic tone can provide a therapeutic benefit toa patient disease or disorder selected from the group consisting of:diabetes; sleep apnea; heart failure; and combinations of these.

The reduction in diastolic pressure can be greater than the reduction insystolic pressure. For example, the reduction in diastolic pressure canbe at least 2 mmHg more than the reduction in systolic pressure, or atleast 4 mmHg more than the reduction in systolic pressure, orapproximately 5 mmHg more than the reduction in systolic pressure.

The reduction in diastolic pressure can be at least 5 mmHg, or at least10 mmHg, or at least 15 mmHg, or at least 18 mmHg. The reduction insystolic pressure can be at least 5 mmHg, or at least 10 mmHg, or atleast 13 mmHg.

The reduction in diastolic pressure can correlate to the diastolicpressure present prior to the creation of the flow pathway. For example,the reduction in diastolic pressure can be proportional to the diastolicpressure present prior to the creation of the flow pathway.

The flow pathway can comprise a fistula. The flow pathway can bepositioned relatively proximate a kidney of the patient. The flowpathway can be positioned at a location that is infrarenal.

The first vascular location can comprise an artery selected from thegroup consisting of: aorta; axillary; brachial; ulnar; radial;profundal; femoral; iliac; popliteal; and carotid. The second vascularlocation can comprise a vein selected from the group consisting of:inferior vena cava; saphenous; femoral; iliac; popliteal; brachial;basilic; cephalic; medial forearm; medial cubital; axillary; andjugular.

The first vascular location can comprise a chamber of the heart. In someembodiments, the first vascular location comprises the left atrium andthe second vascular location comprises the right atrium. In someembodiments, the first vascular location comprises the left ventricleand the second vascular location comprises the coronary sinus. In someembodiments, the first vascular location comprises the aorta and thesecond vascular location comprises a vein, and the flow pathway cancomprise a graft positioned between the aorta and the vein.

The method can further comprise dilating the flow pathway. The flowpathway can be dilated by inflating a balloon in the flow pathway. Thedilation can be performed at a diameter between 3 mm and 5 mm, such asat a diameter of approximately 4 mm.

The method can further comprise performing a flow pathway assessmentprocedure. The flow pathway assessment procedure can comprise performingan anatomical measurement, for example a measurement selected from thegroup consisting of: a flow pathway diameter measurement; a flow pathwaylength measurement; a measurement of the distance between an artery andvein comprising the flow pathway; a measurement of the distance betweenthe flow pathway and a vessel sidebranch; and combinations of these. Theflow pathway assessment procedure can comprise performing an assessmentof at least one of flow in the flow pathway or flow proximate the flowpathway, for example a flow assessment selected from the groupconsisting of: flow through the flow pathway; flow in a vessel segmentproximate the flow pathway; flow measured using Doppler Ultrasound; flowmeasured using angiographic techniques; and combinations of these. Theflow pathway assessment procedure can comprise an assessment of apatient physiologic condition, for example a condition selected from thegroup consisting of: cardiac output; blood pressure such as systolicand/or diastolic blood pressure; respiration; a blood gas parameter;blood flow; vascular resistance; pulmonary resistance; an averageclotting time assessment; serum creatinine level assessment; andcombinations of these.

The method can further comprise placing an implant in the flow pathway.The implant can comprise an anastomotic clip. The implant can comprisean implant selected from the group consisting of: suture; staple;adhesive; and combinations of these. The implant can comprise at least aportion that is biodegradable.

The method can further comprise modifying the flow pathway. Themodification can comprise dilating at least a portion of the flowpathway. In an embodiment, where the method further comprises placing ananastomotic clip in the flow pathway, the modification can be performedafter the placement of the anastomotic clip. The modification can beperformed at least one week after the creating of the flow pathway. Themodification can comprise modifying a flow parameter selected from thegroup consisting of: flow pathway cross sectional diameter; flow pathwayaverage cross sectional diameter; flow pathway flow rate; flow pathwayaverage flow rate; diastolic pressure after flow pathway creation;diastolic pressure change after flow pathway creation (e.g. as comparedto diastolic pressure prior to flow pathway creation); systolic pressureafter flow pathway creation; systolic pressure change after flow pathwaycreation (e.g. as compared to systolic pressure prior to flow pathwaycreation); ratio of diastolic to systolic pressure after flow pathwaycreation; difference between diastolic pressure and systolic pressureafter flow pathway creation; and combinations of these. The modificationcan comprise a flow modification procedure selected from the groupconsisting of: increasing flow through the flow pathway; decreasing flowthrough the flow pathway; increasing the diameter of at least a segmentof the flow pathway; decreasing the diameter of at least a segment ofthe flow pathway; removing tissue proximate the flow pathway; blocking asidebranch proximate the flow pathway; and combinations of these.

The method can further comprise creating a second flow pathway between athird vascular location and a fourth vascular location. The firstvascular location can comprise an artery and the third vascular locationcan comprise the same artery. The second vascular location can comprisea vein and the fourth vascular location can comprise the same vein. Thesecond flow pathway can comprise a fistula. The second flow pathway canbe created at least twenty four hours after the creation of the firstflow pathway.

According to another aspect of the present inventive concepts, a systemfor treating hypertension in a patient comprises a needle deliverydevice constructed and arranged to place a vessel-to-vessel guidewirefrom a starting vessel to a target vessel and a flow creation deviceconstructed and arranged to be advanced over the vessel-to-vesselguidewire and to create a flow pathway between the starting vessel andthe target vessel, where the system is constructed and arranged to causea reduction in diastolic pressure.

The system can be further constructed and arranged to treat a patientdisease or disorder selected from the group consisting of: chronicobstructive pulmonary disease, congestive heart failure, lung fibrosis,adult respiratory distress syndrome; lymphangioleiomytosis; pulmonaryhypertension; sleep apnea such as sleep apnea due to hypoxemia orhypertension; and combinations of these.

The system can be further constructed and arranged to cause a reductionin systolic blood pressure. The system is further constructed andarranged to cause a reduction in diastolic pressure to an extent atleast approximating a reduction in systolic pressure. The system can befurther constructed and arranged to cause a reduction in diastolicpressure to an extent greater than a reduction in systolic pressure.

The needle delivery device can comprise an advanceable needle. Theneedle delivery device can comprise a needle with a gauge between 20 and24, such as an approximately 22 gauge needle. The needle delivery devicecan comprise a curved needle. The needle delivery device can furthercomprise a marker indicating the direction of curvature of the curvedneedle, for example a marker selected from the group consisting of: flatsurface, visible marker, line, textured surface, and combinations ofthese. The needle delivery device can further comprise a sheathconstructed and arranged to slidingly receive the curved needle. Theneedle can comprise a proximal end and a hub positioned on said proximalend. The hub can be constructed and arranged to be advanced to advancethe curved needle out of the sheath. The needle delivery device cancomprise a needle comprising a shaped memory alloy, for example a nickeltitanium alloy.

The system can further comprise a vessel-to-vessel guidewire constructedand arranged to be placed from the starting vessel to the target vesselby the needle delivery device. The vessel-to-vessel guidewire cancomprise a wire with an outer diameter approximating 0.018″. Thevessel-to-vessel guidewire can comprise a marker, for example a markerpositioned to indicate the fistula location. The vessel-to-vesselguidewire can comprise a distal portion and a mid portion, where the midportion can comprise a construction different than the construction ofthe distal portion, for example the mid portion can comprise a stiffnessgreater than the stiffness of the distal portion.

The flow creation device can comprise a balloon catheter configured todilate tissue positioned between the first vascular location and thesecond vascular location. The flow creation device can comprise anenergy delivery device constructed and arranged to deliver energy totissue positioned between the first vascular location and the secondvascular location.

The flow creation device can comprise a clip deployment cathetercomprising an anastomotic clip. The clip deployment catheter cancomprise a handle, and the handle can comprise a control constructed andarranged to deploy the anastomotic clip. The control can comprise abutton. The handle can comprise a safety position for the control, forexample, the handle can comprise a longitudinal axis, and the controlcan be constructed and arranged to be moved relatively perpendicular tosaid longitudinal axis to transition from the safety position to a firstready to deploy position. The clip can comprise at least two distalarms, and the handle can be constructed and arranged to allow anoperator to move the control from a first ready to deploy position to afirst deployed position, where the movement causes the at least twodistal arms to be deployed. The handle can comprise a longitudinal axis,and the control can be moved relatively parallel to said longitudinalaxis to transition from the first ready to deploy position to the firstdeployed position. The handle can be constructed and arranged to allowan operator to move the control from the first deployed position to asecond ready to deploy position. The control can be moved relativelyperpendicular to the longitudinal axis to transition from the firstdeployed position to the second ready to deploy position. The clip cancomprise at least two proximal arms, and the handle can be constructedand arranged to allow an operator to move the control from the secondready to deploy position to a second deployed position, where themovement causes the at least two proximal arms to be deployed. Thecontrol can be moved relatively parallel to said longitudinal axis totransition from the second ready to deploy position to the seconddeployed position.

The clip deployment catheter can comprise an outer sheath, and thecontrol can be constructed and arranged to be moved from a firstposition to a second position to cause movement of the outer sheath. Theclip deployment catheter can be constructed and arranged such thatmovement of the control to the second position causes a tactile feedbackevent to occur. The clip can comprise multiple deployable arms, and theclip deployment catheter can be constructed and arranged such thatmovement of the control to the second position causes at least one armto be deployed.

At least one of the clip deployment catheter or the clip can comprise atleast one marker constructed and arranged to rotationally position theclip. The marker can be constructed and arranged to be oriented towardthe target vessel prior to deployment of the clip. The marker can beoriented based on a patient image, for example a real-time fluoroscopyimage. The clip can comprise a swing arm for deployment in the targetvessel, and the marker can be positioned in alignment with the swingarm. The clip deployment catheter can comprise a distal portion and saiddistal portion can comprise the clip and the marker, for example wherethe marker is proximate the clip. The clip deployment catheter cancomprise a proximal portion and said proximal portion can comprise themarker, for example the clip deployment catheter can comprise a handleand the marker can be positioned on the handle.

At least one of the clip deployment catheter or the clip can comprise atleast one marker constructed and arranged to longitudinally position theclip at the fistula location. The marker can indicate the distal and/orproximal end of the clip.

The clip can comprise multiple deployable arms, and the clip deploymentcatheter can be constructed and arranged to deploy at least one of saiddeployable arms and subsequently recapture said one of said deployablearms.

The clip deployment catheter can be constructed and arranged to berotated and simultaneously deployed from the starting vessel to thetarget vessel over the vessel-to-vessel guidewire.

The clip deployment catheter can comprise a projection constructed andarranged to mechanically engage the clip. The projection can comprise apin. The clip deployment catheter can further comprise a secondprojection constructed and arranged to mechanically engage the clip.

The system can further comprise a flow pathway maintaining implant. Theflow pathway maintaining implant can comprise an anastomotic clip. Theclip can comprise a plurality of distal arms and a plurality of proximalarms, where the distal arms can be independently deployable from theproximal arms. In some embodiments, the clip comprises four deployabledistal arms and four deployable proximal arms. The clip can comprisenickel titanium alloy. The clip can comprise multiple deployable arms,and at least two arms can comprise a marker, for example a radiopaquemarker. The flow pathway maintaining implant can comprise suture; one ormore staples; adhesive; at least a portion that comprises biodegradablematerial; and combinations of these.

The system can further comprise a venous system introducer. The venoussystem introducer can be constructed and arranged to access the startingvessel. The venous system introducer can comprise an 11 Frenchintroducer. The venous system introducer can comprise a beveled distaltip, for example comprising an angle between 20° and 50°, such as anangle of approximately 30°. The venous system introducer can comprise amarker proximate the beveled distal tip, for example a radiopaquemarker. The venous system introducer can comprise a proximal portioncomprising a marker, where the marker can be aligned with the beveleddistal tip. The venous system introducer can comprise a distal portionand an expandable element mounted to the distal portion, for examplewhere the expandable element comprises a balloon. The expandable elementcan be constructed and arranged to prevent inadvertent advancement ofthe introducer into the target vessel. The venous system introducer canbe constructed and arranged to stabilize the starting vessel.

The system can further comprise an arterial system introducer. Thearterial system introducer can be constructed and arranged to access thetarget vessel. The arterial system introducer can comprise a 4 Frenchintroducer.

The system can further comprise a target wire constructed and arrangedfor positioning in the target vessel. The target wire can comprise ahelical distal portion. The target wire can comprise a radiopaque distalportion.

The system can further comprise a flow pathway modifying device. Theflow pathway modifying device can comprise an expandable element. Theexpandable element can be constructed and arranged to expand to adiameter between 3 mm and 5 mm, such as a diameter of approximately 4mm. The expandable element can comprise a balloon. The expandableelement can comprise at least one of an expandable cage or radiallydeployable arms. The flow modifying device can comprise a deviceselected from the group consisting of: an over the wire deviceconstructed and arranged to be delivered over a vessel-to-vesselguidewire as described herein; an expanding scaffold configured toincrease or otherwise modify flow pathway geometry such as an expandableballoon; an energy delivery catheter such as a catheter configured todeliver energy to tissue proximate a flow pathway; an agent deliverycatheter such as a catheter configured to deliver an agent such as apharmaceutical agent or an adhesive such as fibrin glue; andcombinations of these.

The system can further comprise a patient imaging apparatus. The patientimaging apparatus can comprise a fluoroscope and/or an ultrasoundimager.

According to another aspect of the present inventive concepts, a systemfor creating a fistula between a starting vessel and a target vessel ata fistula location in a patient comprises a vascular introducer; aneedle delivery device; a vessel-to-vessel guidewire constructed andarranged to be placed from the starting vessel to the target vessel bythe needle delivery device; an anastomotic clip; and a clip deploymentcatheter constructed and arranged to deploy the anastomotic clip.

The system can be further constructed and arranged to treat a patientdisease or disorder selected from the group consisting of: chronicobstructive pulmonary disease, congestive heart failure, lung fibrosis,adult respiratory distress syndrome; lymphangioleiomytosis; pulmonaryhypertension; sleep apnea such as sleep apnea due to hypoxemia orhypertension; and combinations of these.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate various embodiments of thepresent inventive concepts, and, together with the description, serve toexplain the principles of the invention. In the drawings:

FIG. 1 is a flow chart of a method for treating a patient by creating aflow pathway between a first vascular location and a second vascularlocation, consistent with the present inventive concepts.

FIG. 2 is a schematic view of a system for creating a flow pathway in apatient, consistent with the present inventive concepts.

FIGS. 3A through 3D are a set of steps for implanting an anastomoticclip, consistent with the present inventive concepts.

FIGS. 3E and 3F are a graph of blood pressure measurements recorded frompatients receiving a flow pathway, consistent with the present inventiveconcepts.

FIG. 4 is a table of average change in blood pressure recorded frompatients receiving a flow pathway, consistent with the present inventiveconcepts.

FIG. 5 is a flow chart of a method for treating a patient with a flowpathway, consistent with the present inventive concepts.

FIG. 6 is an angiographic view of a patient's vein and artery prior toadvancement of a needle into the artery, consistent with the presentinventive concepts.

FIGS. 6A, 6B and 6C are anatomical views of three different needletrajectory paths, consistent with the present inventive concepts.

FIG. 7 is a perspective view of an anastomotic clip, consistent with thepresent inventive concepts.

DETAILED DESCRIPTION OF THE DRAWINGS

Reference will now be made in detail to the present embodiments of theinventive concepts, examples of which are illustrated in theaccompanying drawings. Wherever practical, the same reference numberswill be used throughout the drawings to refer to the same or like parts.

The terminology used herein is for the purpose of describing particularembodiments and is not intended to be limiting of the inventiveconcepts. As used herein, the singular forms “a,” “an” and “the” areintended to include the plural forms as well, unless the context clearlyindicates otherwise.

It will be further understood that the words “comprising” (and any formof comprising, such as “comprise” and “comprises”), “having” (and anyform of having, such as “have” and “has”), “including” (and any form ofincluding, such as “includes” and “include”) or “containing” (and anyform of containing, such as “contains” and “contain”) when used herein,specify the presence of stated features, integers, steps, operations,elements, and/or components, but do not preclude the presence oraddition of one or more other features, integers, steps, operations,elements, components, and/or groups thereof.

It will be understood that, although the terms first, second, third etc.may be used herein to describe various limitations, elements,components, regions, layers and/or sections, these limitations,elements, components, regions, layers and/or sections should not belimited by these terms. These terms are only used to distinguish onelimitation, element, component, region, layer or section from anotherlimitation, element, component, region, layer or section. Thus, a firstlimitation, element, component, region, layer or section discussed belowcould be termed a second limitation, element, component, region, layeror section without departing from the teachings of the presentapplication.

It will be further understood that when an element is referred to asbeing “on” or “connected” or “coupled” to another element, it can bedirectly on or above, or connected or coupled to, the other element orintervening elements can be present. In contrast, when an element isreferred to as being “directly on” or “directly connected” or “directlycoupled” to another element, there are no intervening elements present.Other words used to describe the relationship between elements should beinterpreted in a like fashion (e.g., “between” versus “directlybetween,” “adjacent” versus “directly adjacent,” etc.). When an elementis referred to herein as being “over” another element, it can be over orunder the other element, and either directly coupled to the otherelement, or intervening elements may be present, or the elements may bespaced apart by a void or gap.

The term “and/or” where used herein is to be taken as specificdisclosure of each of the two specified features or components with orwithout the other. For example “A and/or B” is to be taken as specificdisclosure of each of (i) A, (ii) B and (iii) A and B, just as if eachis set out individually herein.

Referring now to FIG. 1, a flow chart for selecting and treating apatient by creating a fistula or other flow pathway between a firstvascular location in the patient's arterial system and a second vascularlocation in the patient's venous system is illustrated, consistent withthe present inventive concepts. In STEP 10, a patient assessment isperformed, such as to diagnose the patient and determine if a fistulashould be created in the patient. A patient can be selected based on adisease or disorder which is diagnosed in STEP 10 or previously. In someembodiments, a patient diagnosed with hypertension is selected toreceive a fistula. Alternatively or additionally, a patient selected toreceive a fistula can have a disease or disorder selected from the groupconsisting of: chronic obstructive pulmonary disease (COPD), congestiveheart failure, lung fibrosis, adult respiratory distress syndrome;lymphangioleiomytosis; pulmonary hypertension; sleep apnea such as sleepapnea due to hypoxemia or hypertension; and combinations of these.

In STEP 20, a fistula creation procedure is performed on the patient. Insome embodiments, the fistula creation procedure is performed asdescribed in reference to FIG. 5 herebelow. In some embodiments, thefistula creation procedure is performed using a system of devices andcomponents similar to system 100 of FIG. 2 described herebelow. Thefistula is created between a first vascular location in the arterialsystem, such as an artery, and a second vascular location in the venoussystem, such as a vein. The fistula creation procedure can include theplacement of a vessel-to-vessel guidewire between a starting vessel suchas a vein, and a target vessel such as an artery. In these embodiments,the fistula can be created using one or more fistula creation devicesthat are advanced over the vessel-to-vessel guidewire. An anastomoticclip or other implant can be placed into the fistula via a clipplacement device advanced over the vessel-to-vessel guidewire.Alternatively, a fistula can be created without an anastomotic clip,such as through the use of energy (e.g. radiofrequency energy), sutureor staple (e.g. via an over-the-wire suture or staple delivery device),and/or a tissue treatment such as an adhesive (e.g. fibrin glue) coatingof the tissue surrounding or otherwise proximate the fistula. One ormore fistula treatment or modification procedures can be performed usingfistula treatment or modification devices advanced over thevessel-to-vessel guidewire, such as a fistula modification performed inSTEP 40 herebelow.

In some embodiments, a fistula or other flow pathway is created betweenan artery and a vein at a location distal to the renal arteries (i.e. aninfrarenal location). In some embodiments, a fistula or other flowpathway is created proximate a kidney. Numerous locations for thefistula or other flow pathway can be selected, such as a fistula locatedbetween an artery and vein as described in reference to FIG. 5herebelow. Alternatively or additionally, a flow pathway can be createdbetween a chamber of the heart and a second vascular location, such asbetween the left atrium and the right atrium or between the leftventricle and the heart's coronary sinus. Alternatively or additionally,arterial blood can be diverted to the venous system by way of a flowpathway comprising a bypass graft, such as is described in applicant'sco-pending application U.S. Non-Provisional application Ser. No.11/151,802, entitled “Methods for Providing Oxygenated Blood to VenousCirculation”, filed Jun. 13, 2005, the contents of which areincorporated by reference herein in its entirety.

During the fistula creation procedure and/or in a subsequent fistulamodification procedure, a fistula dilation procedure can be performed.In some embodiments, an anastomotic clip is placed in the fistula and aballoon catheter is used to dilate the fistula and anastomotic clipsimultaneously. In some embodiments, the balloon comprises a diameter ofapproximately 3 mm to 5 mm, such as a diameter of approximately 4 mm.

In STEP 30, a fistula assessment procedure can be performed. STEP 30 canbe performed in the same clinical procedure as STEP 20, and/or in asubsequent clinical procedure such as a procedure at least twenty-fourhours after completion of STEP 20, or at least 1 week, at least 1 month,and/or at least 6 months after completion of STEP 20. In someembodiments, the assessment performed in STEP 30 includes one or moreanatomical measurements, such as a measurement selected from the groupconsisting of: a fistula diameter measurement; a fistula lengthmeasurement; a measurement of the distance between the artery and veincomprising the fistula; a measurement of the distance between thefistula and a vessel sidebranch; and combinations of these. In someembodiments, the assessment performed in STEP 30 comprises an assessmentof flow, such as a flow assessment selected from the group consistingof: flow through the fistula; flow in a vessel segment proximate thefistula; flow measured using Doppler Ultrasound; flow measured usingangiographic techniques; and combinations of these. In some embodiments,the assessment performed in STEP 30 comprises an assessment of a patientphysiologic condition, such as an assessment of a physiologic conditionselected from the group consisting of: cardiac output; blood pressuresuch as systolic and/or diastolic blood pressure; respiration; a bloodgas parameter; blood flow; vascular resistance; pulmonary resistance; anaverage clotting time assessment; serum creatinine level assessment; andcombinations of these.

In STEP 40, one or more fistula parameters can be modified. STEP 40 canbe performed in the same clinical procedure as STEP 20, and/or in asubsequent clinical procedure such as a procedure at least twenty-fourhours after completion of STEP 20, or at least 1 week, at least 1 month,and/or at least 6 months after completion of STEP 20. In someembodiments, STEP 30 and STEP 40 are performed in the same clinicalprocedure (e.g. both in the same clinical procedure as STEP 20 or bothin a subsequent clinical procedure). In some embodiments, one or morepatient or fistula parameters to be modified are selected from the groupconsisting of: fistula cross sectional diameter; fistula average crosssectional diameter; fistula flow rate; fistula average flow rate;diastolic pressure after fistula creation; diastolic pressure changeafter fistula creation (e.g. as compared to diastolic pressure prior tofistula creation); systolic pressure after fistula creation; systolicpressure change after fistula creation (e.g. as compared to systolicpressure prior to fistula creation); ratio of diastolic to systolicpressure after fistula creation; difference between diastolic pressureand systolic pressure after fistula creation; and combinations of these.

Fistula modification procedures can include but are not limited to:increasing flow through the fistula; decreasing flow through thefistula; increasing the diameter of at least a segment of the fistula;decreasing the diameter of at least a segment of the fistula; removingtissue proximate the fistula; blocking a sidebranch proximate thefistula; and combinations of these. A fistula modifying device caninclude one or more devices selected from the group consisting of: anover the wire device constructed and arranged to be delivered over avessel-to-vessel guidewire as described herein; an expanding scaffoldconfigured to increase or otherwise modify fistula geometry such as anexpandable balloon; an energy delivery catheter such as a catheterconfigured to deliver energy to tissue proximate a fistula; an agentdelivery catheter such as a catheter configured to deliver an agent suchas a pharmaceutical agent or an adhesive such as fibrin glue; andcombinations of these.

In some embodiments, a second fistula is created, such as using thetechniques of STEP 20 described hereabove. The second fistula can becreated in the same clinical procedure as STEP 20 (in which the firstfistula is created), or in a subsequent clinical procedure such as aprocedure performed at least twenty-four hours after completion of STEP20, or at least 1 week, at least 1 month, and/or at least 6 months aftercompletion of STEP 20. A second fistula can be created due to inadequatetherapy provided by the first fistula, and/or if the first fistula hasinsufficient flow (e.g. becomes non-patent). A second fistula can becreated due to formation of a vascular (e.g. venous) stenosis proximatethe first fistula. In these embodiments, the first fistula can bereversed (e.g. closed), such as through the placement of a covered stentgraft in the vein or artery that covers the fistula, or otherfistula-occlusive procedure.

The method of FIG. 1 can be performed using real-time imaging, such asreal-time imaging provided by a fluoroscope and/or an ultrasound imagingdevice.

The method of FIG. 1 can be performed to decrease peripheral vascularresistance, such as to decrease infrarenal vascular resistance (e.g.below the kidneys or in a manner to include the great vessels of theaorta and/or the inferior vena cava). Alternatively or additionally, themethod can be performed to achieve a physiologic change selected fromthe group consisting of: increased oxygen delivery by the arterialsystem; increased blood volume; increased proportion of blood flow tothe descending aorta; increased blood flow to the kidneys; increasedblood flow outside the kidneys; increased cardiac output; andcombinations of these. The method can be constructed and arranged toprevent any significant chronic increase in heart rate. Alternatively oradditionally, the method can be constructed and arranged to prevent adecrease in cardiac function. Alternatively or additionally, the methodcan be constructed and arranged to avoid undesired adverse effects tothe kidneys, such as by avoiding the adverse effects that can beencountered in a renal denervation procedure, such as stenosis, lostautonomic control and/or vessel intima damage.

In some embodiments, the method is performed to increase oxygenationand/or flow rates associated with the patient's chemo-receptors, such asto cause a therapeutic change to vascular resistance. In someembodiments, the method is performed to affect or otherwise modify thepatient's central sympathetic tone. Modifications to central sympathetictone can be performed to reduce systolic and/or diastolic blood pressure(e.g. mean systolic and/or mean diastolic blood pressure), and/or totreat other patient diseases and conditions such as diabetes, sleepapnea, or heart failure.

In some embodiments, the method of FIG. 1 is constructed and arranged tocause a reduction in diastolic blood pressure that is equal to orgreater than a concurrent reduction in systolic blood pressure, such asare presented in Table 3 described herebelow. In some embodiments, themethod is constructed and arranged to reduce the diastolic pressure morethan the systolic pressure by an amount of at least 2 mmHg, at least 4mmHg or approximately 5 mmHg. In some embodiments, the method isconstructed and arranged to reduce the diastolic pressure by at least 5mmHg, such as a reduction of at least 10 mmHg, at least 15 mmHg orapproximately 18 mmHg. In some embodiments, the method is constructedand arranged to reduce the systolic pressure by at least 5 mmHg, such asa reduction of at least 10 mmHg or approximately 13 mmHg. In someembodiments, the method is constructed and arranged to cause a reductionin blood pressure to a level at or below 130/90 mmHg.

The method of FIG. 1 and associated clinical testing has been performedby applicant in a study in patients with hypertension and COPD. In thestudy, the patients with hypertension received a significant andbeneficial drop in blood pressure as a result of the fistula creation.Twenty four of the patients studied had systolic pressure greater than130 mmHg. In each patient, a 4 mm fistula was created to shunt bloodfrom the right iliac artery to the right iliac vein. Cardiac output wasmeasured before and after the procedure, and blood pressure was recordedbefore the procedure and again at 3, 6, 9 and 12 months. The creation ofa fistula in the iliac region increased cardiac outputs by 41% (p<0.01),with a mean percentage change of 44%. An unexpected outcome was thatpatients with high blood pressure soon had a substantial drop in boththeir systolic and diastolic blood pressures. In previously performedlarge population studies, a 10 mmHg drop in systolic blood pressure hasbeen associated with a 40% reduction in risk of stroke mortality and a30% reduction in risk of death due to coronary disease. A year after theprocedure, average drop in systolic blood pressure was 13 mmHg lower (SD17; p<0.01) and the average drop in diastolic blood pressure was 18.4mmHg (SD 12; p<0.0001). The only significant adverse effect of theprocedure was the development of venous stenosis in the iliac vein abovethe site of the fistula. This adverse event occurred in four subjects,but was corrected by placing a covered stent in the iliac vein over thefistula. Detailed information on the study is provided immediatelyherebelow.

Methods & Participating Patients

Patients were selected based on several inclusion and exclusioncriteria, including the ability to undergo arteriovenous fistulacreation, GOLD Stage II or greater COPD, and participants were without acurrent exacerbation of COPD and were on stable medication for a minimumof 4 weeks prior to enrollment. The criteria for exclusion includedpulmonary arterial hypertension (a mean Pulmonary Arterial Pressuregreater than 35 mmHg), obesity (Body Mass Index greater than 31 kg·m-2male or 32 kg·m-2 female), liver cirrhosis, recent stroke or heartfailure (within 6 months), unstable coronary artery disease, andmalignant cancer that might adversely affect the subject's safety. Alarge group of patients (n=67) had an arteriovenous fistula created aspart of a multi-center international study of arteriovenous fistulacreation in patients with severe COPD. In addition to parametersconcerned with exercise capacity and pulmonary function, subjects werealso evaluated for office-based blood pressure and hemodynamic measuresduring cardiac catheterization at baseline and follow-up. Of particularnote were twenty-four subjects with high blood pressure (subjects who,in spite of anti-hypertensive therapy had systolic blood pressurerecordings greater than 130 mmHg at baseline) who were not known to havea secondary cause of hypertension. Blood pressure and hemodynamicchanges in those twenty-four hypertensive subjects are reported herein.Patients underwent percutaneous arteriovenous fistula creation using ananastomotic clip such as anastomotic clip 160 of FIG. 2 describedherebelow. Assessment included physical examination, clinic based bloodpressure recordings, and cardiac catheterization to measure cardiacoutput, oxygen delivery, and both pulmonary and systemic vascularresistances.

Procedure

In each procedure, an anastomotic clip was deployed in the iliac regionto create an iliac arteriovenous fistula. Vascular femoral venous andarterial access was obtained using standard interventional techniques.FIGS. 3A and 3B illustrate the 7 French anastomotic clip delivery deviceused, including the anastomotic clip which was implanted. In someembodiments, the anastomotic clip delivery device comprises device 150,and the anastomotic clip comprises device 160, each of FIG. 2 herebelow.In FIG. 3C, an angiogram of the iliac artery A and iliac vein V prior toshunt creation is illustrated. A vessel targeting wire CW, such as wire120 of FIG. 2, outlines the iliac artery, and a venogram confirms vesselproximity and target crossing location for the creation of thearteriovenous fistula. A 22 gauge crossing needle, such as a needle ofdeployment device 140 of FIG. 2 herebelow, is placed into the vein overa guidewire and through an 11 French introducer device, not shown butsuch as introducer 110 also of FIG. 2 herebelow. The 22 gauge crossingneedle has been advanced through the wall of the iliac vein into theiliac artery, and a guidewire advanced through a lumen of the needle andinto the artery. In the procedure, the needle was subsequently removedand the anastomotic clip delivery system tracked across the puncturesite. The anastomotic clip was then deployed so that the expanded armsof the anastomotic clip attached to the inner walls of the iliac arteryand iliac vein, and the retention arms maintained the anastomotic clipin the proper position (deployed position shown in FIG. 3D). Afterremoval of the delivery system, a 4-mm balloon catheter was insertedinto the center of the anastomotic clip and inflated to expand theanastomotic clip to a 4-mm diameter. The balloon was then deflated andremoved. An angiogram confirmed the patency of the fistula. Subjectswere prescribed aspirin and compression stockings after the procedure.

Baseline measurements consisted of vital signs, physical examination andcardiac catheterization. Follow-up assessments were performed at 3, 6,9, and 12 months, which consisted of office blood-pressure measurement,physical examination, and surveillance for adverse events. Bloodpressures were recorded in an office setting and in accordance withstandard Joint National Committee VII guidelines. Subjects alsounderwent repeat cardiac catheterization 3 to 6 months after thecreation of the fistula. Cardiac output was measured in all but fivesubjects using a thermodilution catheter technique. In five subjects thebaseline and follow-up cardiac output were measured using the Ficktechnique.

Statistical Analysis

All blood pressure analyses were performed post-hoc. Changes inoffice-based blood pressure were analyzed over 12 months of follow-upand compared with baseline blood pressure by repeated measures analysisof variance with pair-wise comparison of significant values. To assessthe hemodynamic effect of arteriovenous fistula creation, hemodynamicmeasures were compared between baseline and repeat cardiaccatheterization (between 3 and 6 months after the creation of thefistula) using paired t-tests. Adverse events were also recorded. A pvalue of less than 0.05 was regarded as statistically significant.Multiple linear regression analysis was performed to determine whetheran association exists between changes in hemodynamic measures andchanges in office based blood pressure and age, gender, baseline heartrate, and baseline severity of COPD.

Results—Characteristics of the Patients:

While testing the creation of an iliac arteriovenous fistula using apercutaneously deployed nitinol anastomotic clip in sixty-seven patientswith COPD, twenty-four (13 male) subjects were included who had both asystolic blood pressure greater than 130 mmHg and severe COPD (meanpost-bronchodilator FEV1=30% predicted). The procedure was successful inall cases. Their demographic details are contained in Table 1. Twothirds of patients (n=16) had a systolic blood pressure greater than 140mmHg at baseline, while 21% had a systolic blood pressure greater than160 mmHg There was no gender or race/ethnic based difference in outcome.Arterial blood pressure at enrollment was 145/86 mmHg (SD 12/13), with aheart rate of 91 beats per minute (SD 16). Patients took, on average, 2anti-hypertensive medications, with (29%) receiving anangiotensin-converting enzyme inhibitor, (17%) an angiotensin IIreceptor blocker, (17%) beta-blockers, (25%) calcium-channel blockers,and (8%) direct vasodilators. Almost half (46%) of the hypertensivepatients also took diuretics as shown in Table 1 immediately herebelow.

TABLE 1 Baseline demographics of the 24 subjects with severe COPD andhypertension who underwent creation of the arteriovenous fistula. Dataare presented as mean (standard deviation). Number of subjects 24 Ageyears 65 (6)  Male gender 54% Body mass index kg · m⁻² 25 (5)  Cigaretteconsumption (pack years) 47 (25) Systolic blood pressure mmHg 145 (12) Diastolic blood pressure mmHg 86 (13) Mean arterial blood pressure mmHg105 (12)  Serum creatinine mg/dl 0.84 (.26)  Diuretic 46% ACE inhibitor29% Angiotensin receptor blocker 17% Beta-blocker 17% Vasodilator(nitrate)  8% Calcium channel blocker 25% Post-bronchodilator FVC (%predicted) 68 (22) Post-bronchodilator FEV₁ (% predicted) 30 (11) PaO₂mmHg on Room air 63 (9)  PaCO₂ mmHg on Room air 42 (6) 

Results—Blood Pressure Lowering Effect:

The average blood pressure measurements were: 145/86 mmHg, 139/76 mmHg,130/71 mmHg, 132/74 mmHg, and 132/67 mmHg at baseline, 3 months, 6months, 9 months, and 12 months respectively, as shown in FIGS. 3E and3F. By the end of the study period (12 months) the systolic bloodpressure was reduced from 145 (SD 12) mmHg to 132 (SD 18) mmHg (p<0.01)and the diastolic blood pressure was reduced from 86 (SD 13) mmHg to 67(SD 13) mmHg (p<0.0001). Multiple comparison testing revealedsignificant differences in systolic blood pressure between baseline and3 months, baseline and 6 months, baseline and 9 months, and baseline and12 months and a significant difference was also seen between 3 monthsand 12 months, as shown in FIG. 3E and FIG. 4. Multiple comparisontesting revealed significant differences in diastolic blood pressurebetween baseline and 6 months, baseline and 9 months, and baseline and12 months, as is shown in FIG. 3F and FIG. 4. Multivariable analysisshowed a significant association between baseline diastolic bloodpressure and changes in diastolic pressure at 12 months (p<0.02) butfailed to show a clear association between blood-pressure reduction andany of the following: age, gender, baseline heart rate, baselineseverity of COPD (PaO2 and FEV1). At baseline, patients were taking anaverage of two anti-hypertensive medications, which did not changeduring follow-up.

Results—Hemodynamic Changes Assessed During Cardiac Catheterization:

Cardiac catheterization revealed increases in cardiac output (from 6 (SD2) liters/min at baseline to 8.4 (SD 3) liters/min, p<0.001) and oxygendelivery (from 1091(SD 432) ml/min to 1441 (SD 518) ml/min, p<0.001),accompanied by reductions in mean arterial pressure (106 (SD 12) mmHg to97 (SD 12) mmHg, p<0.001), systemic vascular resistance (1457 (SD 483)dynes to 930 (SD 335) dynes, p<0.001), and pulmonary vascular resistance(190 (SD 117) dynes to 140 (SD 77) dynes, p<0.01). Although no changewas detected in the right atrial pressures and heart rates, there weresmall but significant increases in both the pulmonary arterial pressure(25 (SD 5) mmHg at baseline to 29 (SD 6) mmHg at follow-up, p<0.01), andthe pulmonary capillary wedge pressure (12.2 (SD 5) mmHg at baseline to15.5 (SD 7) mmHg at follow-up, p=0.01). Multivariable regressionrevealed an association between changes in cardiac output and changes inpulmonary vascular resistance (p<0.05) and between changes in cardiacoutput and changes in systemic vascular resistance (p<0.05). Changes inpulmonary capillary wedge pressure (PCWP) were associated with changesin systemic vascular resistance (p<0.05) but were not associated withchanges in pulmonary vascular resistance (PVR).

The median procedure time (from skin to skin) was 53 minutes (range 20minutes to 2 hours and 15 minutes). Among the twenty-four patients whounderwent arteriovenous fistula creation, the procedure was completedwithout complication in twenty of the patients. Within 7 days of theprocedure, two patients developed pseudoaneurysm at the femoral accesssite, which was successfully treated with manual compression; onepatient developed mild chest pressure and chest pain, which resolved;and one patient developed a clot around the fistula which resolved afteranti-coagulant therapy. Late adverse events included four patients whodeveloped deep venous thrombosis (resolved with anti-coagulation) andanother patient in whom the shunt was closed in a separate clinicalprocedure (at 11 months), because of a lack of clinical improvement.Four subjects developed a venous stenosis of the iliac vein cephalad tothe device. Two of these cases were initially treated with dilatation,however the stenosis recurred, and they were then successfully treatedwith stent placement. The other pair was successfully treated with stentplacement without recurrence. In one case, the stent was undersized,resulting in dislodgement and migration into the right ventricle. Thestent was retrieved and repositioned in the left iliac vein with nosequelae, and the venous stenosis was successfully treated with anappropriately sized self-expanding stent. There was no death during the12-month follow-up period. In patients whose baseline creatinine levelwas higher than 1.0 mg/dl (n=4, average creatinine was 1.29 mg/dl, range1.05 to 1.51 mg/dl), there was a significant increase in glomerularfiltration rate, eGFR (MDRD). Their eGFR at 12 months was increased to67 (SD 18) ml/min from 54 (SD 18) ml/min at baseline, (p=0.02).

DISCUSSION

The study provides significant data demonstrating the efficacy of themethods, systems and devices of the present inventive concepts to treathypertension. Patients suffering from arterial hypertension thatreceived a peripheral arteriovenous fistula had a significant reductionin their blood pressure. A year after the procedure, their systolicblood pressures are an average of 13 mmHg lower, and their diastolicpressures are an average of 18 mmHg lower. In fact, the higher thediastolic pressure before the procedure, the greater is the drop indiastolic pressure. The number of patients with hypertension (a systolicblood pressure greater than 140 mmHg) is halved (16 to 8).

The methods, systems and device of the present inventive conceptsprovide a painless percutaneous procedure producing rapid reductions inblood pressure. Deployment of the device employs iliofemoral vascularaccess with a catheter guidance system, and (through a series ofcrossing needles and dilators) creation of a 4 mm fistula between theiliac artery and iliac vein. The fistulas remained patent (100% patencyrate at 1 year) and is remarkably well tolerated, even in these elderlypatients with advanced lung disease.

Blood pressure lowering effect is not the only hemodynamic effect ofthis procedure. Our hemodynamic data obtained via cardiaccatheterization correlate to increased cardiac output and oxygendelivery, and the study results demonstrated significant reductions inpulmonary vascular resistance and systemic vascular resistance. The dropin pulmonary vascular resistance appears to be associated with changesin cardiac output, rather than increases in pulmonary capillary wedgepressure or increases in mixed venous oxygen content (see Table 2herebelow). This drop in pulmonary vascular resistance is supported byapplicant's work on pulmonary hypertensive disease in rats, which showedthat the creation of a modest arteriovenous shunt attenuates rather thanaccelerates the development of pulmonary vascular disease.

TABLE 2 Hemodynamic values at baseline and on repeat cardiaccatheterization post insertion of the arteriovenous anastomotic clip (n= 23). Baseline Repeat* p value Heart rate (bpm)  91 (16)  92 (16) 0.85Mean arterial pressure mmHg 106 (12)  97 (12) 0.001 Right atrialpressure mmHg  8 (4) 9.5 (4)  0.17 Cardiac output (liters/min)  6 (2)8.4 (3)  <0.001 Oxygen delivery (ml. min.⁻¹) 1091 (432) 1441 (518)<0.001 Systemic vascular resistance dynes 1457 (483)  930 (335) <0.001Mean pulmonary arterial 25 (5) 29 (6) <0.01 pressure mmHg Mixed venousoxygen 73 (6) 79 (5) <0.001 saturation % Pulmonary capillary wedge 12.2(5)   15.5 (7)   0.01 pressure mmHg Pulmonary vascular resistance  190(117) 140 (77) <0.01 dynes *Repeat cardiac catheterization was performedbetween 3 and 6 months after creation of an arteriovenous fistula.

Table 3 herebelow represents ambulatory blood pressure data for eightpatients who received the fistula creation procedure of the presentinventive concepts. The data includes daytime and nighttime bloodpressures for each patient at baseline and 1 month, 3 months and 6months after the fistula creation procedure. Patient 1 and Patient 3daytime blood pressure significantly decreased at nighttime over sixmonths as compared with baseline blood pressure. Patient 2 is a diabeticon multiple medications and saw a significant decrease in daytime bloodpressure by six months. Patient 4 received Tegretol (carbamaepine) andLipitor (atorvastatin) between baseline and three months. Patient 5 isresistant to all hypertension medications. Patient 6 nighttime bloodpressure significantly decreased at three months such that the patient'sblood pressure decreased from daytime to nighttime. Patient 7 diastolicblood pressure significantly dropped in the daytime and nighttime by 1month. Patient 8 systolic blood pressure entered normal range in thedaytime and nighttime at 1 month.

TABLE 3 Ambulatory Blood Pressure (BP) Daytime/Nighttime Changes for 8Patients Baseline Baseline 1 Mo 1 Mo 3 Mo 3 Mo 6 Mo 6 Mo Patient DayNight Day Night Day Night Day Night 1 162/98 150/90 159/78 132/60 158/80140/69 160/75 135/60 2 159/72 126/64 158/67 134/59 135/55 126/53 133/57124/53 3 152/86 138/73 151/76 133/64 144/77 127/63 143/71 127/61 4163/76 147/72 148/65 139/62 158/71 154/68 — — 5  189/113  181/108 197/103 166/88  192/110 182/99 — — 6 135/69 131/62 129/59 125/61 138/69119/60 — — 7 143/86 149/89 145/71 146/74 — — — — 8 140/74 133/68 127/60126/61 — — — —

Table 4 herebelow represents average serum creatinine data for threepatients who received the fistula creation procedure of the presentinventive concepts. The data includes serum creatinine levels for threepatients having Stage II Hypertension and elevated serum creatininelevels for four patients at baseline at baseline and three months, sixmonths, nine months, and twelve months after the fistula creationprocedure. The data indicates a sustained decrease in serum creatininelevels representative of increased kidney perfusion, thus improved renalfunction. The analysis showed no correlation between change in serumcreatinine and weight over the course of the twelve months follow up.

TABLE 4 Average serum creatinine levels for 3 Patients representative ofincreased kidney perfusion and improved renal function Baseline 3 Mo 6Mo 9 Mo 12 Mo Serum Creatinine 1.10 0.96 0.95 0.85 0.90 Levels (mg/dL)Stage II Hypertension Serum Creatinine 1.29 1.30 1.10 1.00 1.04 Levels(mg/dL) Elevated Levels at Baseline

Table 5 herebelow represents the results from an evaluation of cardiacfunction for patients who received the fistula creation procedure of thepresent inventive concepts. Echocardiogram results demonstrated nochange, and in some cases, an improvement to cardiac function for thosepatients receiving the fistula creation procedure. Control dataindicated a decline in cardiac function for some patients.

TABLE 5 Change in Cardiac Function: Data represented by # ofpatients/total # of patients ROX Device Control 6 Month 12 Month 6 Month12 Month No Change 15/19  11/15  13/20  11/16  Improvement 4/19 3/153/20 1/16 Decline 0/19 1/15 4/20 4/16

Referring now to FIG. 2, a system for creating a fistula or other flowpathway between a first location in a patient's arterial system of apatient (e.g. an artery), and a second location in the patient's venoussystem (e.g. a vein), is illustrated. System 100 comprises a vascularintroducer, first introducer 110, configured to be placed into thepatient to provide access to a starting vessel. System 100 comprisesanother vascular introducer, second introducer 130, configured toprovide access to a target vessel. In some embodiments, the startingvessel is a vein, and the target vessel is an artery. In otherembodiments, the starting vessel is an artery and the target vessel is avein. System 100 can include target wire 120 which comprises helicalsection 121 and is configured to be placed through the second introducer130 and into the target vessel. Target wire 120 can be placed through anelongate tube, catheter 122. System 100 can comprise needle deploymentdevice 140 which is configured to deploy crossing needle 145 (shown inan advanced position in FIG. 2), from the starting vessel and into thetarget vessel. System 100 can include a vessel-to-vessel guidewire 170,which can be placed from the starting vessel to the target vessel vianeedle deployment device 140. System 100 can also include clipdeployment catheter 150, which is configured to deploy anastomotic clip160. System 100 can include a fistula modifying device, such as dilationdevice 180 including balloon catheter 185 and standard angioplastyballoon indeflator 181. System 100 can further comprise imagingapparatus 190, typically a fluoroscope and/or ultrasound imaging deviceused to image one or more device or components of system 100, as well asthe patient's anatomy, during the creation of an arteriovenous fistula.

First introducer 110 is configured to be placed into the patient toprovide access to a starting vessel (e.g. a vein of a patient). In someembodiments, introducer 110 comprises an 11 French vascular introducer.First introducer 110 can comprise beveled tip 111 with an angle rangingfrom 20° to 50°, such as at an angle of approximately 30°. Additionally,system 100 can include a kit comprising an additional introducer havinga second angle providing the clinician or other user (hereinafter“clinician) with more options as may be appropriate for a particularpatient's anatomical geometry. In some embodiments, beveled tip 111comprises a marker, for example, a radiopaque or other visualizablemarker, such that the luminal wall of the starting vessel can be imaged(e.g. when tip 111 is pressed against the vessel wall). The proximalportion of introducer 110 can comprise a contour or marker, such as tobe correlated with or otherwise indicate the alignment of the bevel oftip 111.

Introducer 110 comprises shaft 117 which includes at least one thrulumen. Introducer 110 also comprises port 116, typically a hemostasisvalve, which is fluidly connected to the lumen of shaft 117. A secondport 118, typically a luer connector, is connected to tubing 115 whichin turn is connected to port 116. Introducer 110 can further comprise adilator, not shown but typically an 11 to 13 French dilator used tointroduce and/or pre-dilate tissue receiving introducer 110. Introducer110 can further comprise a radially expandable element, such asexpandable element 119, such as a balloon or expandable cage located onits distal portion. In some embodiments, expandable element 119 can beconfigured to prevent advancement of introducer 110 into the targetvessel. In yet another embodiment, expandable element 119 can beconfigured to stabilize the starting vessel during insertion ofintroducer 110 or another device or component of system 100.

System 100 can comprise second introducer 130 which is configured toprovide access to a target vessel, such as an artery of the patient whenthe starting vessel is a vein. In some embodiments, second introducer130 comprises a 4 French vascular introducer. System 100 comprisestarget wire 120 configured to be placed through second introducer 130and into the target vessel. Target wire 120 can comprise helical section121 configured to be deployed at the site where the fistula is to becreated. Helical section 121 can be configured to provide structure andsupport to the site during a procedure. Additionally, target wire 120can serve as a visual reference during insertion of vessel-to-vesselguidewire 170, as described herebelow.

System 100 can comprise needle deployment device 140. Needle deploymentdevice 140 comprises shaft 141 which slidingly receives advanceablecrossing needle 145, shown in an advanced state. Shaft 141 comprisesshaft hub 142 mounted to its proximal end. Shaft 141 can comprise acurved distal portion as shown. Crossing needle 145 comprises needle hub146 mounted to its distal end. Movement of needle hub 146 relative toshaft hub 142 causes crossing needle 145 to advance and retract withinshaft 141. Needle hub 146 is fully advanced toward shaft hub 142 in theconfiguration of FIG. 2, such that the tip and distal portion ofcrossing needle 145 is fully advanced out of the distal end of shaft141.

Crossing needle 145 can comprise a 20 to 24 gauge needle, such as a 22gauge needle. In some embodiments, the crossing needle comprises acurved distal portion (as shown). The curved distal portions of shaft141 and/or needle 145 can be aimed at the center of the target vesselprior to insertion into the target vessel. The radius of curvature canbe reduced if the clinician has difficulty in aiming the needle tip atthe center of the target vessel prior to insertion. Conversely, theradius of curvature can be increased to sufficiently aim the needle tipat the center of the target vessel. Additionally, the crossing needle145 can comprise a marker, not shown but indicating the direction ofcurvature. Examples of markers include, but are not limited to: a flatsurface, a textured surface; a visualizable marker such as a radiopaquemarker, a magnetic marker, an ultrasonic marker or a visible marker; andcombinations of these. In some embodiments, crossing needle can comprisea shaped memory alloy, for example, nickel titanium alloy. In someembodiments, shaft hub 142 and/or needle hub 146 comprise a marker orother visible demarcation (e.g. a flat portion) which correlates to thedirection of curvature of shaft 141 and/or crossing needle 145,respectively.

System 100 can comprise a guidewire to be placed from the startingvessel to the target vessel, vessel-to-vessel guidewire 170. Guidewire170 is configured to be placed via needle deployment device 140. In someembodiments, vessel-to-vessel guidewire 170 comprises a wire with anouter diameter of approximately 0.018″. Vessel-to-vessel guidewire 170can comprise a marker, not shown but configured to indicate the fistulalocation. In some embodiments, vessel-to-vessel guidewire 170 comprisesa distal portion and a mid portion. Guidewire 170 mid portion cancomprise a different construction than the distal portion. For example,the mid portion of guidewire 170 can be stiffer than the distal portion.

System 100 can comprise clip deployment catheter 150 configured to houseand deploy anastomotic clip 160. Clip 160 comprises a plurality ofdistal arms 161 and a plurality of proximal arms 162, which can bedeployed simultaneously or independently. Clip 160 comprises at leasttwo distal arms 161 and at least two proximal arms 162 configured todeploy and engage the starting vessel and the target vessel. In someembodiments, clip 160 comprises four deployable distal arms 161 and fourdeployable proximal arms 162. Clip 160 can comprise a shaped memoryalloy, such as nickel titanium alloy. In some embodiments, clip 160 isconstructed and arranged as described in applicant's U.S. Pat. No.7,828,814, entitled “Device and Method for Establishing an ArtificialArterio-Venous Fistula”, filed Apr. 4, 2007, the contents of which areincorporated herein by reference in its entirety.

In some embodiments, clip 160 is biodegradable or includes one or morebiodegradable portions (e.g. one or more portions of clip are absorbedor otherwise degrade over time). In some embodiments, clip 160 comprisesa biodegradable anastomotic device such as is described in applicant'sco-pending U.S. Non-Provisional application Ser. No. 12/752,397,entitled “Device and Method for Establishing an Artificial ArteriovenousFistula”, filed Apr. 1, 2010, the contents of which are incorporatedherein by reference in its entirety.

Clip deployment catheter 150 comprises shaft 151. Mounted to theproximal end of shaft 151 is handle 153. On the proximal end of handle153 is port 155, which is operably attached to shaft 151 such that aguidewire can travel from the distal end of shaft 151 to port 155, suchas guidewire 170 after it has been previously placed between a startingvessel and a target vessel as has been described hereabove. Shaft 151comprises one or more tubular portions, such as an inner tubular segmentthat houses clip 160, and an outer tubular segment that covers clip 160but can be retracted to deploy clip 160, such as is described inapplicant's co-pending U.S. Non-Provisional application Ser. No.11/152,621, entitled “Devices for Arterio-Venous Fistula Creation”,filed Jun. 13, 2005, the contents of which is incorporated herein byreference in its entirety.

Handle 153 further includes control 152 (e.g. a button, slide or lever),where control 152 is operably configured to allow an operator to deploydistal arms 161 and/or proximal arms 162 of clip 160, such as viaretraction of an outer tube or sheath portion of shaft 151 that iscovering one or more portions of clip 160. In some embodiments, a clickor other tactile feedback is provided during retraction of a sheathportion of shaft 151. Control 152 can be moved via a stepped orotherwise segmented slot 156. Distal arms 161 can be deployed via movingcontrol 152 from a “first ready to deploy” position to a “firstdeployed” position which can be achieved by moving control 152relatively parallel to the longitudinal axis of handle 153. The at leasttwo proximal arms 162 can be queued to be deployed via moving control152 from the first deployed position to a “second ready to deploy”position. The second ready to deploy position can be achieved by movingcontrol 152 in a direction perpendicular to the longitudinal axis of thehandle. Subsequently, proximal arms 162 can deployed via moving control152 from the second ready to be deployed position to a “second deployed”position via a motion parallel to the longitudinal axis of the handle.In this embodiment, control 152 can include a safety position comprisinga ready to deploy position which can be transitioned by moving control152 in a direction that is perpendicular to the axis of handle 153. Thiscontrol advancement arrangement can prevent inadvertent deployment ofdistal arms 161 and/or proximal arms 162.

In some embodiments, prior to deployment of one or more arms of clip160, introducer 110 can be advanced such that end 111 applies a force tothe wall of the starting vessel. Sufficient force can be applied byintroducer 110 to enable an operator to “seat” the starting vesselagainst the target vessel to assist in properly deployment of clip 160.

In some embodiments, catheter 150 can be configured to recapture distalarms 161 and/or proximal arms 162. For example, clip deployment catheter150 can deploy at least one distal arm 161 and subsequently recapturethe at least one distal arm 161.

Clip deployment catheter 150 and/or clip 160 can further comprise atleast one marker, not shown but typically a radiopaque and/or ultrasonicmarker configured to assist in the rotational positioning of clip 160 atthe fistula location. For example, the marker can be oriented toward thetarget vessel prior to deployment of clip 160. In some embodiments, amarker is included on the distal portion of clip deployment catheter150. In some embodiments, handle 153 comprises one or more markers thatare circumferentially aligned with clip 160 prior to its deployment. Insome embodiments, clip deployment catheter 150 and/or clip 160 compriseat least one marker configured to longitudinally position clip 160 atthe fistula location. In these embodiments, the marker can indicate thedistal and/or proximal end of clip 160.

Clip deployment catheter 150 can further comprise a projection and/orrecess, neither shown but configured to mechanically engage clip 160.The project and/or pin can be used to stabilize clip 160 with shaft 151,such as when an outer tubular portion of shaft 151 is advanced orretracted.

System 100 can comprise dilation device 180 configured to dilate clip160 and/or the fistula. Dilation device 180 can include balloon catheter185, such as a standard angioplasty balloon catheter comprising balloon186. Attached to the proximal end of catheter 185 is indeflator 181,typically a standard balloon indeflator device. Alternatively, balloon186 can comprise a non-balloon expandable such as an expandable cage orradially deployable arms configured to dilate the fistula. Catheter 185is configured to track over a vessel-to-vessel guidewire, such asguidewire 170 placed between a vein and an artery, such that balloon 186is positioned within the fistula (e.g. within clip 160). Typically,dilation device 180 can expand to a diameter of less than fivemillimeters, and more typically to a diameter of approximately fourmillimeters. In some embodiments, a second dilation device 180 isincluded, such as a device configured to expand to a different diameterthan the first dilation device.

System 100 can include patient imaging apparatus 190. Non-limitingexamples of an imaging apparatus include: x-ray; fluoroscope; ultrasoundimager; MRI; and combinations of these. The imaging apparatus can allowthe clinician to track the movement of all components comprising system100 as well as view the position of the starting and target vesselrelative to each other, as described in detail herein.

Referring now to FIG. 5, a flow chart of a method of creating a fistulabetween a starting vessel and a target vessel at a fistula location,consistent with the present inventive concepts is illustrated. In Step510, a procedural planning assessment of a patient is performed. Step520 comprises placing a first introducer into a starting vessel, e.g. avein, and placing a second introducer into a target vessel, e.g. anartery. In Step 530, an angiographic orientation is performed and afistula location is selected. Step 540 comprises placing avessel-to-vessel guidewire between the vein and the artery. Step 550comprises placing an anastomotic clip at the fistula location. In someembodiments, system 100 and/or one or more components of system 100 ofFIG. 2 are used to perform the method of FIG. 5.

The starting vessel can comprise a vein, and can be selected from thegroup consisting of: inferior vena cava (IVC); saphenous; femoral;iliac; popliteal; brachial; basilic; cephalic; medial forearm; medialcubital; axillary; and jugular. The target vessel can comprise anartery, and can be selected from the group consisting of: aorta;axillary; brachial; ulnar; radial; profundal; femoral; iliac; poplitealand carotid. In a preferred embodiment, the starting vessel and targetvessel comprise an external iliac. In an alternate embodiment, thestarting vessel can comprise an artery and the target vessel cancomprise a vein.

Step 510, the first step in the illustrated method of the presentinventive concepts comprises procedural planning. This step comprisesproperly orienting the vein and the artery, meaning a clinician becomesfamiliar with the anatomical orientation of the vein and artery relativeto each other. Understanding the orientation of the vessels with respectto one another can be achieved through analysis of one or more imagesprovided by an imaging apparatus (e.g. a fluoroscope) such as imagingapparatus 190 of FIG. 2. In some embodiments, at least one of the veinor artery has a diameter of at least five millimeters proximate thefistula location. In another embodiment, both the vein and artery have adiameter of at least five millimeters proximate the fistula location.

In Step 520, the method comprises placing a first introducer into thevein. Preferably, the first introducer comprises an 11 French introducerhaving a beveled tip, such as introducer 110 of FIG. 2 describedhereabove. In some instances, the beveled tip of the first introducercan be rotated during insertion into the vein. Rotation of theintroducer can be helpful during insertion into the starting vessel dueto the tendency of the beveled tip to lift and pull back. Additionallyor alternatively, the introducer can be vibrated while it is advancedinto the vein. Step 520 can further comprise pre-dilating the vein witha dilator, preferably a 13 French dilator, prior to placing theintroducer into the vein. Additionally, a second introducer can beplaced into the artery. Preferably, the second introducer comprises a 4French introducer, such as introducer 130 described in FIG. 2 hereabove.The method further comprises placing a target wire into the secondintroducer and then into the artery such that the distal end of thetarget wire is positioned five to ten centimeters past the fistulalocation, and configured to serve as a visual reference to a clinician.The target wire, typically including a helical section, is advanced. Theadvancement can be combined with retracting the introducer such that thehelical section of the wire is deployed at the targeted anastomoticsite.

In Step 530, the method comprises performing angiographic orientationand selecting a fistula location. Choosing the fistula location can bebased upon a lack of thrombus or other soft tissue occlusive matter atthe vascular location, as well as lack of plaque or calcified matter.Preferably, the fistula location is chosen at a location where the veinis less than or equal to three millimeters apart from the artery.Techniques can be used to image the vein and artery in side-by-sideconfigurations as well as overlapping (i.e. on top of each other in theimage) orientations. Rotation of the imaging device 90° can modify theprovided image from a side-by-side image to an overlapping image, andback again. In some embodiments, after a fistula location has beenselected, a clinician can orient the fluoroscope such that the vein andartery are shown overlapping, such as with the vein on top of theartery. In some embodiments, the clinician can position a fluoroscope orother imaging device at an angle to the patient approximating 35° RAO.

In Step 540, the method comprises placing a vessel-to-vessel guidewireinto the vein, such as while the vein and artery are imaged in anoverlapping orientation, as described in Step 530 hereabove. A next stepcomprises placing a needle delivery device over the vessel-to-vesselguidewire and into the vein. The needle delivery device can comprise amarker, as described in FIG. 2 hereabove, such that a clinician canorient the marker toward the artery. The guidewire can be retracted andsubsequently, the needle of the needle delivery device can be advancedtoward the target wire and toward the artery. In some embodiments, thevessel-to-vessel guidewire can be placed through a dilator.

Prior to inserting the crossing needle into the artery, a clinician canaim the needle tip at the center of the artery to ensure desiredengagement of the artery with the needle, such as by rotating theproximal end of the needle or a device containing the needle. In someembodiments, the needle or needle delivery device includes a proximalhub with a demarcation (e.g. a flat portion or a marker) positioned toindicate the orientation of a curved distal portion of the needle, suchas is described in reference to needle deployment device 140 of FIG. 2hereabove. In this operation, a clinician can torque or otherwise rotatethe needle such that the direction of the needle curvature comes intoview on the imaging apparatus (e.g. fluoroscope). Confirming thedirection of needle curvature ensures that the needle is to be advancedin the desired direction, such as into the center of the artery. In someembodiments, a target wire is placed in the target vessel, such astarget wire 170 of FIG. 2 described hereabove. Preferably, the needlecomprises a curved tip, and the radius of curvature can be reduced if aclinician has difficulty in aiming the needle at the center of thetarget vessel prior to insertion. Conversely, the radius of curvaturecan be increased to sufficiently aim the needle tip at the center of thetarget vessel. In some embodiments, the needle delivery catheter isoriented as described in reference to FIG. 6 herebelow.

Additionally, a clinician can confirm that the distal portion of thevessel-to-vessel guidewire is located within the lumen of the artery.Also, the clinician can confirm the vessel-to-vessel guidewire isparallel with the target wire previously placed in the artery. Aclinician can confirm that the needle is positioned within the targetvessel by using a dye injection through the needle. Alternatively oradditionally, a clinician can confirm that the needle is properlypositioned in a target vessel by measuring the pressure in a distalportion of the needle, such as to confirm presence in an artery byconfirming arterial pressure is recorded.

In some embodiments, the needle deployment device is placed into theartery and the guidewire is advanced from the artery into the vein viathe crossing needle. In these embodiments, the anastomotic clip deliverycatheter can also be advanced from artery to vein.

In Step 550, the method comprises placing an anastomotic clip at afistula location. Prior to performing Step 550, placing an anastomoticclip at a fistula location, a user can retract the crossing needle whilemaintaining the position of the target wire. Next, the target wire canbe removed from the second introducer. The target wire can also beremoved after Step 550.

In Step 550, a user can position the vein and artery such that the veinand artery are slightly apart from each other on the image (e.g. notoverlapping). In one embodiment, this can be achieved by rotating afluoroscopy unit 45° to 90° after an overlapping image is obtained (e.g.an image obtained during a dual contrast injection of both the arteryand vein).

Next, the tip of the clip deployment catheter (with a pre-loadedanastomotic clip) can be placed at the fistula site. In this step, aclinician can apply forward pressure and rotate the clip deploymentcatheter. The clip can comprise at least two distal arms and at leasttwo proximal arms that can be deployed simultaneously or independentlyvia a control located on the handle of the catheter.

Step 550 further comprises deploying the anastomotic clip in thefistula, such as is described in detail in reference to clip deploymentcatheter 150 of FIG. 2 hereabove. The clip distal arms are deployed bymoving a control on the clip deployment catheter from a ready to deployposition to a first deployed position, which can be achieved by movingthe control relatively parallel to the longitudinal axis of the handle.Prior to deploying the proximal arms of the clip, a clinician canretract the first introducer to the fistula location and seat the veinagainst the artery. The clip deployment catheter can comprise a markerlocated on its distal end. Using this marker, a clinician can pull theclip deployment catheter back such that the marker is aligned with thedistal end of the first introducer.

In a next operation of STEP 550, the proximal arms can be queued to bedeployed via moving the control from a first deployed position to asecond ready to deploy position. The ready to deploy position can beachieved by moving the control in a direction perpendicular to thelongitudinal axis of the handle. Subsequently, the proximal arms candeployed via moving the control from the second ready to be deployedposition to the second deployed position via a motion parallel to thelongitudinal axis of the handle. In this embodiment, the controlincludes a safety position comprising a ready to deploy position whichcan be transitioned by moving the control in a direction that isperpendicular to the axis of the handle. This control arrangement canprevent inadvertent deployment of the distal and/or proximal arms. Afterdeployment of the proximal arms, a clinician can retract the firstintroducer from the anastomosis site, such as a retraction ofapproximately two to three centimeters, followed by retracting the clipdeployment catheter.

The method can further comprise dilating the fistula via a balloon orother expandable member. For example, a clinician can track a ballooncatheter over the target wire and inflate the balloon. In a typicalembodiment, the balloon catheter comprises a diameter of four to fivemillimeters and can be inflated via a four millimeter by one and onehalf centimeter non-conforming balloon and indeflator device. Theballoon then can be deflated and retracted out of the implant.

The method can further comprise verifying clip patency. This can beachieved via a contrast/saline solution injected into the secondintroducer. A clinician can then remove all devices once it is confirmedthat the clip is positioned as desired.

The method can further comprise placing a second anastomotic clip, suchas a second anastomotic clip 160 of FIG. 2 described hereabove.Alternatively or additionally, the method can further comprise creatinga second flow pathway between, such as a second fistula created duringthe same clinical procedure or a subsequent clinical procedure. Thesecond flow pathway can be between the same two vascular locations asthe first flow pathway, or one or both of the second flow pathwayvascular locations can be different (e.g. a different vein and/orartery).

Referring now to FIG. 6, an angiographic view of a patient's vein andartery prior to advancement of a needle into the artery is illustrated,such as may be performed in Step 540 of the method of FIG. 5 describedhereabove, consistent with the present inventive concepts. In theillustrated embodiment, a clinician has oriented an imaging device (e.g.a fluoroscope or other imaging device of FIG. 1), such that the segmentsof vein and artery at a proposed fistula location are overlapping (i.e.on top of each other in the image). The clinician has placed a targetwire 120 into a patient's artery such that the helical portion of wire120 is positioned at the proposed fistula location. Additionally, needledeployment device 140 has been advanced intraluminally through the veinas shown such that its distal end is proximal to the proposed fistulalocation. A next step comprises advancing needle 145 toward the helicalportion of wire 120 at the proposed fistula location.

Prior to insertion of needle 145 into the artery, a clinician can rotateneedle deployment device 140 such that the direction of the needledeployment device 140 curvature is viewed (i.e. a non-linear, curvedsegment is visualized) on the imaging apparatus. Confirming thedirection of curvature ensures that needle 145 is to be advanced in thedesired direction, such as into the center of the artery. For example,if a clinician rotates needle deployment device 140 such that its tip ispositioned as shown in FIG. 6A or 6C, a clinician will be aiming to anoff-center location of the patient's artery. If a clinician rotatesneedle deployment device 140 such that its tip is positioned as shown ifFIG. 6B, needle 145 will subsequently be advanced into the relativecenter of the patient's artery. The radius of curvature of a needledeployment device 140 can be reduced (e.g. by manual reshaping or byselected a different needle deployment device 140) if a clinician hasdifficulty in aiming needle 145 at the center of the artery prior toinsertion. Conversely, the radius of curvature of needle deploymentdevice 140 can be increased to create a more desirable needle 145advancement trajectory.

Referring now to FIG. 7, a perspective view of an anastomotic clip isillustrated, consistent with the present inventive concepts. Clip 160can comprise at least two distal arms 161 and at least two proximal arms162. In the illustrated embodiment, clip 160 comprises four distal arms161 and four proximal arms 162.

Clip 160 can be formed from a single tube of resilient material, such asnickel titanium alloy, spring steel, glass or carbon composites orpolymers, or pseudoelastic (at body temperature) material such as nickeltitanium alloy or comparable alloys and polymers, by laser cuttingseveral closed-ended slots along the length of the tube (leaving theextreme distal and proximal edges of the tube intact) and cuttingopen-ended slots from the longitudinal center of the tube through thedistal and proximal edges of the tube. The open-ended slots are cutbetween each pair of closed-end slots to form a number of loops joinedat the center section by waist segments. Many other fabricationtechniques can be utilized, for example, clip 160 can be made of severalloops of wire welded together at the waist section.

After the tube is cut as described above, it is formed into its eventualresiliently expanded configuration. In this configuration, the loopsturn radially outwardly from the center section, and evert toward thecenter plane of the center section, thus forming clinch members, i.e.distal arms 161 and proximal arms 162, in the form of arcuate, everted,petaloid frames at either end of the loop, extending from the generallytubular center section formed by waist segments. For clarity, the termeverted is used here to mean that the arc over which the petaloid frameruns is such that the inside surface of clip 160 faces radiallyoutwardly from the cylinder established by the tube.

Once clip 160 has resiliently expanded to the extent possible given itsimpingement upon the walls of the starting vessel and the target vessel,the center section can be further expanded by plastic deformation. Thiscan be accomplished by inflating a balloon, not shown, within the centersection and expanding the center section beyond its elastic orsuperelastic deformation range. By plastically deforming the centersection of clip 160, the center section becomes more rigid and able towithstand the compressive force of the walls of the starting and targetvessels.

As illustrated, the construction provides several pairs oflongitudinally opposed (that is, they bend to come into close proximityto each other, and perhaps but not necessarily, touch) and aligned (theyare disposed along the same longitudinal line) distal arms 161 andproximal arms 162. Overall, the petaloid frames of distal arms 161 forma “corolla,” analogous to the corolla of a flower, flange or rivetclinch, which impinges on the starting vessel wall and preventsexpulsion into the target vessel, and the petaloid frames of proximalarms 162 form a corolla, flange or rivet clinch (this clinch would beanalogous to a rivet head, but it is formed like the clinch afterinsertion of the rivet), which impinges on the target vessel wall andprevents the expulsion of clip 160 into the target vessel. Also, thecentral section forms a short length of rigid tubing to keep the fistulaopen. The resilient apposition of the at least two distal arms 161 andat least two proximal arms 162 will securely hold clip 160 in place byresiliently clamping the walls of the starting vessel and the targetvessel, even over a considerable range of wall thickness or “griprange.”

The respective lengths of arms 161 and 162 can be variably sized tomaximize or optimize the stability of clip 160 with respect to thevessels when deployed between adjacent vessels. Moreover, varying thelengths of the respective arms can further provide additionaladvantages. For instance, the arms which are shortened in length canfacilitate the positioning and securement of clip 160 between thevessels by allowing for the relatively shorter member to swing intoposition within the vessel lumen during deployment, as described infurther detail below. Additionally, a shorter member can provide for aminimized implant size when placed against the vessel interior wall forsecurement as well as a mitigating any physiologic reaction to theimplant, e.g., a reduction in thrombosis, etc. Additionally, arms 161and/or 162 which are lengthened relative to other arms can provide forincreased clip stability by increasing the amount of force appliedagainst the tissue walls.

Moreover, arms having different lengths can additionally place theadjacent vessels in tension such that the vessel walls are drawn towardsone another and arms 161 and/or 162 contact the vessel luminal walls tostabilize not only clip 160 within the vessels but also the vessels withrespect to one another. Additionally, having one or more arms, such asdistal arms 161, sized to have a length shorter than its respectiveapposed clinch member can also facilitate the deployment and/orpositioning of distal arms 161 within the vessel since the shorterlength clinch members can more easily “swing” through an arc within thevessel lumen without contacting the interior walls. Arms with differinglengths can further be configured to align along different planes whendeployed to facilitate vessel separation, if so desired.

Clip 160 can further comprise at least one marker, not shown, configuredto rotationally position the clip at the fistula location. For example,a marker can be oriented toward the target vessel prior to deployment ofclip 160. Alternatively or additionally, a marker can be oriented basedupon a patient image, e.g. a real-time fluoroscopy image. In yet anotherembodiment, clip 160 can comprise at least one marker configured tolongitudinally position the clip at the fistula location. A marker canindicate the distal and/or proximal end of clip 160.

Clip 160 can further comprise holes 164 configured to engage a clipdelivery catheter projection such as to allow the shaft of the clipdeployment catheter, not shown, to be retracted while clip 160 remainspositioned in the distal portion of the shaft. In one embodiment, holes164 are constructed and arranged about the clip asymmetrically such thatclip 160 can be attached in the proper orientation.

While the preferred embodiments of the devices and methods have beendescribed in reference to the environment in which they were developed,they are merely illustrative of the principles of the inventions.Modification or combinations of the above-described assemblies, otherembodiments, configurations, and methods for carrying out the invention,and variations of aspects of the invention that are obvious to those ofskill in the art are intended to be within the scope of the claims. Inaddition, where this application has listed the steps of a method orprocedure in a specific order, it may be possible, or even expedient incertain circumstances, to change the order in which some steps areperformed, and it is intended that the particular steps of the method orprocedure claim set forth herebelow not be construed as beingorder-specific unless such order specificity is expressly stated in theclaim.

What is claimed is:
 1. A system for treating hypertension in a patient,comprising: a needle delivery device constructed and arranged to place avessel-to-vessel guidewire from a starting vessel to a target vessel; aflow creation device constructed and arranged to be advanced over thevessel-to-vessel guidewire and to create a flow pathway between thestarting vessel and the target vessel; wherein the system is constructedand arranged to cause a reduction in diastolic pressure, wherein theflow creation device comprises a clip deployment catheter comprising ananastomotic clip and wherein the clip deployment catheter comprises ahandle and the handle comprises a control constructed and arranged todeploy the anastomotic clip.
 2. The system of claim 1 wherein thecontrol comprises a button.
 3. The system of claim 1 wherein the handlecomprises a safety position for the control.
 4. The system of claim 3wherein the handle comprises a longitudinal axis and wherein the controlis constructed and arranged to be moved relatively perpendicular to saidlongitudinal axis to transition from the safety position to a firstready to deploy position.
 5. The system of claim 1 wherein the clipcomprises at least two distal arms, and wherein the handle isconstructed and arranged to allow an operator to move the control from afirst ready to deploy position to a first deployed position, wherein themovement causes the at least two distal arms to be deployed.
 6. Thesystem of claim 5 wherein the handle comprises a longitudinal axis andwherein the control is moved relatively parallel to said longitudinalaxis to transition from the first ready to deploy position to the firstdeployed position.
 7. The system of claim 5 wherein the handle isconstructed and arranged to allow an operator to move the control fromthe first deployed position to a second ready to deploy position.
 8. Thesystem of claim 7 wherein the control is moved relatively perpendicularto the longitudinal axis to transition from the first deployed positionto the second ready to deploy position.
 9. The system of claim 7 whereinthe clip comprises at least two proximal arms, and wherein the handle isconstructed and arranged to allow an operator to move the control fromthe second ready to deploy position to a second deployed position,wherein the movement causes the at least two proximal arms to bedeployed.
 10. The system of claim 7 wherein the control is movedrelatively parallel to said longitudinal axis to transition from thesecond ready to deploy position to the second deployed position.
 11. Thesystem of claim 1 wherein the clip deployment catheter comprises anouter sheath and wherein control is constructed and arranged to be movedfrom a first position to a second position to cause movement of theouter sheath.
 12. The system of claim 11 wherein the clip deploymentcatheter is constructed and arranged such that movement of the controlto the second position causes a tactile feedback event to occur.
 13. Thesystem of claim 11 wherein the clip comprises multiple deployable arms,and wherein the clip deployment catheter is constructed and arrangedsuch that movement of the control to the second position causes at leastone arm to be deployed.
 14. The system of claim 1 further comprising avenous system introducer, wherein the venous system introducer comprisesa distal portion and an expandable element mounted to the distalportion.
 15. The system of claim 14 wherein the expandable element isconstructed and arranged to prevent inadvertent advancement of theintroducer into the target vessel.